Thiamine

It's been stated that oral thiamine trials have improved cognitive function in patients with AD. That paper refers to a prior study which hasn't been cited in subsequent literature and is behind a paywall. It would be good to check the strength of this study given subsequent papers not appearing to reinforce its view.

A cursory review of additional literature suggests why the Bredesen Protocol specifically recommends using the benfotiamine, a thiamine precursor see patent application. It doesn't appear that thiamine itself has been shown to reduce cognitive impairment in humans:

-- A 2015 review, Role of dietary protein and thiamine intakes on cognitive function in healthy older people: a systematic review., concludes: 'A lack of experimental [human] studies in this area prevents the translation of these dietary messages for optimal cognitive functioning and delaying the decline in cognition with advancing age.'

-- A 2016 discussion, Vitamin B1 (thiamine) and dementia, describes the close connection between thiamine deficiency and hypometabolism of glucose in the brain and concludes: 'Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.'

However, these preliminary mouse and cell culture studies describe benfotiamine's beneficial effects, to be confirmed in humans:

-- Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice (2010) states: 'Thiamine treatment exerts little beneficial effect in [Alzheimer's] patients... In the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms... These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.' [Emphasis added]

-- Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells (2015 in cell cultures) concludes: 'Our results open the possibility for benfotiamine application in neurodegenerative conditions which show hyper-reactive microglia, such as Alzheimer's, Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis. Further research on animal model studies are warranted in order to evaluate benfotiamine capacity to mitigate the microglial component of pathology of neurological diseases.'

Keeping in mind that the efficacy of Dr. Bredesen's protocol is thought to result from the synergistic effects of its components, it appears further studies in humans may be required to show conclusively that thiamine or benfotiamine supplementation on their own help prevent or reverse Alzheimer's-associated cognitive decline.

While ensuring optimal thiamine status using benfotiamine would seem to be a safe intervention to help address Alzheimer's-related pathologies, two cautionary notes are worth keeping in mind:

1. Thiamine appears to have a complex relationship with cancer, sometimes facilitating tumor growth and other times reducing it. [Needs elucidation]

2. Benfotiamine does not appear to have been studied at length for toxic affects. [Needs cite]